Breast cancer is the most common cancer diagnosed in the U.S. and the second leading cause of cancer related death of women. Fortunately, breast cancer mortality has been declining since the 1990s, mainly due to the introduction of mammography screening at the early 1980s. Presently, mammography is used for widespread screening aimed at early diagnosis of breast cancer. However, mammography uses X-rays for breast imaging which poses significant cumulative risks of initiating and promoting breast cancer due to radiation exposure. Moreover, since the image quality depends on the breast's structure, mammography is primarily suitable for women approaching menopause and post-menopausal women. Young women who are at risk of developing breast cancer (e.g., women with a family history of breast cancer and/or BRCA mutations) cannot obtain a conclusive diagnosis based on mammography screening alone. Another population for which mammography is less suitable is women who are undergoing treatment for breast cancer. The treatment causes irreversible changes to the structure of the breast, which often leads to obscure breast images. Thus, monitoring breast cancer using mammography is often not reliable.
Other available techniques for early diagnosis and monitoring of breast cancer include magnetic resonance imaging (MRI) and ultrasound imaging. However, it has been shown that ultrasound cannot identify breast tumors unambiguously. In addition, although the sensitivity of MRI to breast tumors is high, its specificity to breast tumors is significantly lower in comparison to that of mammography. This leads to false positive results causing anxiety to patients and subjecting healthy women to unnecessary biopsies and other invasive follow-up tests.
Breath analysis has long been recognized as a reliable technique for diagnosing certain medical conditions through the detection of volatile organic compounds (VOCs). The composition of VOCs in exhaled breath is dependent upon cellular metabolic processes and it includes, inter alia, saturated and unsaturated hydrocarbons, oxygen containing compounds, sulfur containing compounds, and nitrogen containing compounds.
In exhaled breath of patients with cancer, elevated levels of certain VOCs including, volatile C4-C20 alkane compounds, specific monomethylated alkanes as well as benzene derivatives were found (Phillips et al., Cancer Biomark., 3(2), 2007, 95). The breath methylated alkane contour (BMAC) demonstrated differences between healthy volunteers and women with an abnormal mammogram whose biopsies were negative for breast cancer (Phillips et al., The Breast Journal, 9(3), 2003, 184). Since the composition of VOCs in exhaled breath of women with breast tumors differs from that of healthy women, measuring the VOC composition of breath samples can be used to diagnose cancer. Phillips et al. (Breast Cancer Research and Treatment, 99, 2006, 19) reported the use of five VOCs, namely 2-propanol, 2,3-dihydro-1-phenyl-4(1H)-quinazolinone, 1-phenyl-ethanone, heptanal, and isopropyl myristate for predicting breast cancer using a fuzzy logic model. Recently, a combination of specific volatile biomarkers in breath samples and a multivariate algorithm were used to identify women with breast cancer (Phillips et al., J. Breath Res., 4, 2010, 026003).
Gas-sensing devices for the detection of VOCs in breath samples of cancer patients have recently been applied. Such devices perform odor detection through the use of an array of cross-reactive sensors in conjunction with pattern recognition algorithms. The array of cross-reactive sensors produces a unique response pattern upon exposure to VOCs, said pattern is then analyzed using pattern recognition algorithms in order to glean information on the identity of the different VOCs and their composition.
Films composed of nanoparticles capped with an organic coating (“NPCOCs”) as gas-sensing devices are disclosed in e.g. U.S. Pat. Nos. 5,571,401, 5,698,089, 6,010,616, 6,537,498, 6,746,960, 6,773,926; Patent Application Nos. WO 00/00808, FR 2,783,051, US 2007/0114138; and in Wohltjen et al. (Anal. Chem., 70, 1998, 2856), and Evans et al. (J. Mater. Chem., 8, 2000, 183).
U.S. Pat. No. 7,052,854 discloses systems and methods for ex-vivo diagnostic analysis using nanostructure-based assemblies comprising a nanoparticle, a means for detecting a target analyte/biomarker, and a surrogate marker. The sensor technology is based on the detection of the surrogate marker which indicates the presence of the target analyte/biomarker in a sample of a bodily fluid.
EP 1,215,485 discloses chemical sensors comprising a nanoparticle film formed on a substrate, the nanoparticle film comprising a nanoparticle network interlinked through linker molecules having at least two linker units. The linker units are capable of binding to the surface of the nanoparticles and at least one selectivity-enhancing unit having a binding site for reversibly binding an analyte molecule. A change of a physical property of the nanoparticle film is detected through a detection means.
WO 2009/066293 to one of the inventors of the present invention discloses a sensing apparatus for detecting volatile and non-volatile compounds. The apparatus comprises sensors of cubic nanoparticles capped with an organic coating. Further disclosed are methods of use thereof in detecting certain biomarkers for diagnosing various diseases and disorders including cancer.
WO 2010/079490 to one of the inventors of the present invention discloses a sensor array comprising conductive nanoparticles characterized by a narrow particle size distribution capped with an organic coating of varying thickness for detecting VOCs indicative of various types of cancer.
There is an unmet need for the unambiguous distinction between malignant tumors and benign tumors, using non-invasive techniques. There further remains a need for a fast responsive sensor array which provides sensitivity as well as selectivity for specific VOCs indicative of benign or malignant tumors for diagnosis, prognosis and monitoring various types of cancer.